Overview: Molecular and Cellular Pathogenesis in Alcoholism. The UNC NIAAA Alcohol Research Center (ARC) fosters interdisciplinary collaborative research on alcoholism, alcohol abuse and the impact of alcohol on health and disease - exactly the goal of an NIAAA ARC. The UNC Bowles Center for Alcohol Studies (CAS) provides a foundation of administrative support and dedicated space for alcohol research. Across ARC components molecular signaling, synaptic networks, neurocircuitry and psychopathology are investigated in models of binge drinking. The scope of these studies requires the Center mechanism to integrate the multiple signaling systems and neurocircuits that underlie complex addiction-like behaviors. The UNC ARC is a catalyst of discovery that promotes collaboration, expands use of new methods and scientific knowledge through regular research meetings, scientific seminars, core research services, annual clinical conferences, pilot projects and through stimulation of interest in the effects of alcohol on health across the University and State. Training and mentoring of students and junior faculty contribute to scholarly interactions and successful laboratory research programs through the ARC. Health professional and youth curricula promote interest in science and knowledge that contribute to improved health. The ARC synergizes with existing investigator funding to promote interactions among multidisciplinary investigators focused on molecular mechanisms of ethanol-related behavioral and tissue pathology. The ARC Specific Aims are to investigate mechanisms of alcohol-induced behavioral, molecular, cellular and neural circuit pathogenesis and to disseminate information on alcohol to health professionals and youth. Research components investigate hypotheses on ethanol-induced regulation of signaling kinases, receptor expression and trafficking, cytokine and peptide gene induction, changes in brain networks and circuitry as well as alcohol induced mood, behavior and drug taking as addiction-like behavioral pathologies. By conducting focused investigations that integrate molecular signaling mechanisms across neural networks and neurocircuitry, the ARC creates synergies that promote and catalyze discoveries. This ARC proposal continues a research focus on molecular and cellular mechanisms with a new emphasis on dysfunctional brain networks and neurocircuitry, a theme at the cutting edge of neuroscience. The ARC will conduct, promote, support, and mentor research on alcoholic pathology and educate broad groups of health professionals and youth in North Carolina.